The long range objective of this research is to use neurophysiological and psychophysical techniques to develop a better understanding of pain perception. This is a grant proposal to continue studies of peripheral neural mechanisms of pain sensation. The intent is to acquire knowledge of acute pain mechanisms and also to understand how pain is enhanced in disease states. This type of analysis has been productive in advancing the diagnosis and treatment of pain in patients in our prior grant period, and promises to do so in the future. Understanding of perception ultimately requires a correlative analysis of events within the nervous system, and measures of sensation. The response of primary nociceptive afferents, obtained from single fiber recordings in the anesthetized monkey, will be correlated with the response of human subjects, based on ratings of subjective magnitude, when both are exposed to the same stimuli. The plan is to continue investigations into the role of nociceptors in signalling the pain from normal skin as well as to continue neurophysiological and psychophysical studies of the mechanisms of hyperalgesia. The specific goals are: (1) To study the role of type II A-fiber nociceptors in pain sensation; (2) To investigate the response of myelinated and unmyelinated nociceptors to controlled mechanical stimuli; (3) To research the signal integration that occurs as a result of the branching structure of the nociceptive receptor; (4) To model the population response of nociceptors to stimuli applied to one locus; (5) To determine whether nociceptor sensitization may account for the mechanical hyperalgesia that occurs in the zone of primary hyperalgesia; (6) To determine the peripheral neural basis for pain due to capsaicin, the pungent ingredient in hot peppers used in studies of secondary hyperalgesia; (7) To perform psychophysical studies of secondary hyperalgesia in normal human subjects in order to help delineate the peripheral and central neural mechanisms of hyperalgesia; and finally, (8) To perform psychophysical studies of hyperalgesia in patients with chronic neuropathic pain and compare these findings with the studies of secondary hyperalgesia in normal subjects.